Obsessive Compulsive Disorder (OCD) is a serious mental illness that affects millions of people throughout the world. Existing therapies for OCD show limited efficacy, can possess troubling side effects, and often require long-term treatment. Discovery of a new treatment for OCD would have considerable scientific value and commercial value. The hallucinogen psilocybin has shown preliminary efficacy against OCD, however even if further research on this compound is positive, FDA approval for psilocybin could be problematic. In Phase One we propose to synthesize carefully selected psilocybin analogs. The pharmacology of these compounds will be evaluated both in vitro and in vivo. From this project we specifically aim to discover one or more psilocybin analogs showing efficacy in an animal model for OCD comparable to that of the existing therapies. Such a result will strongly support continuation in Phase Two. The long-term goal of this project is to discover new, improved treatments for OCD. PROPOSED COMMERCIAL APPLICATION: Discovery of a novel, improved therapy for obsessive compulsive disorder could alleviate suffering for many people worldwide and would have very substantial commercial potential.